Indapamide retard - instructions for use, dose, side effects, contraindications

Excipients: hypromellose (hydroxypropylmethylcellulose) 17 mg; kollidone SR 7.5 mg, including: [polyvinyl acetate 6 mg, povidone 1.425 mg, sodium lauryl sulfate 0.06 mg, silicon dioxide colloidal anhydrous 0.015 mg]; Copovidone 6.6 mg; silicon dioxide colloidal anhydrous 1.2 mg; lactose monohydrate (milk sugar) 69.9 mg; magnesium stearate 1.3 mg; microcrystalline cellulose 25 mg;

auxiliary substances for the preparation of a film shell: Opadrai II white 4 mg, including: [polyvinyl alcohol 1.6 mg; macrogol (polyethylene glycol 3350) 0.808 mg; talc 0.592 mg; titanium dioxide 1 mg].

Description:

The tablets covered with a film membrane of white or almost white color, round, biconcave. On the cross-section - almost white.

Pharmacotherapeutic group:diuretic

ATX: & nbsp

C.03.B.A.11 Indapamide

Pharmacodynamics:

Indapamide - a derivative of sulfonamide, by its pharmacological properties is close to thiazide diuretics (violation of reabsorption of sodium ions in the cortical segment of the Henle loop). Increases the allocation of kidney ions of sodium, chlorine and, to a lesser extent, potassium and magnesium ions, which is accompanied by an increase in diuresis and an antihypertensive effect. The hypotensive effect persists for 24 hours against a background of a single dose, with a moderate increase in diuresis.

Antihypertensive activity is associated with improving the elastic properties of large arteries, reducing arterial and general peripheral vascular resistance. Indapamide reduces left ventricular hypertrophy.Thiazide and thiazide-like diuretics at a certain dose reach a plateau of therapeutic effect, while the incidence of side effects continues to increase with a further increase in the dose of the drug. Therefore, do not increase the dose of the drug, if the recommended dose does not achieve a therapeutic effect.

Indapamide does not affect the content of lipids in the blood plasma (triglycerides, low density lipoproteins, high density lipoproteins); does not affect the metabolism of carbohydrates, including those in patients with diabetes mellitus.

Pharmacokinetics:

Suction

After oral administration, it is quickly and completely absorbed from the gastrointestinal tract; bioavailability is high (93%). Eating somewhat slows the rate of absorption, but does not affect the amount of absorbed substance. The maximum concentration in the blood plasma is achieved 12 hours after ingestion of a single dose. At repeated receptions of fluctuation of concentration of a preparation in a blood plasma in an interval between receptions of two doses decrease.

Distribution

Connection with blood proteins - 79%. The half-life is 14-24 hours (on average, 18 hours).Passes through gistogematicheskie barriers (including placental), excreted in breast milk. The equilibrium concentration is achieved after 7 days of taking the drug. When you re-receive cumulation is not observed.

Metabolism

Indapamide is excreted as inactive metabolites, mainly by the kidneys (70%), and through the intestine (22%).

Patients belonging to the high-risk group

In patients with renal insufficiency, the pharmacokinetics of the drug does not change.

Indications:

Arterial hypertension.

Contraindications:

- Hypersensitivity to indapamide, other derivatives of sulfonamide or to any of the excipients;

- severe form of renal failure (creatinine clearance less than 30 ml / min);

- hepatic encephalopathy or severe liver dysfunction;

- gand apokalemia;

- pregnancy, lactation;

- age under 18 years (effectiveness and safety not established);

- simultaneous reception of drugs that extend the interval QT;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:

In case of violations of the liver and / or kidney function, violation of water-electrolyte balance, hyperparathyroidism, patients with an increased interval QT on ECG or receiving co-therapy, in diabetes mellitus in the stage of decompensation, hyperuricemia (especially accompanied by gout and urate nephrolithiasis).

Pregnancy and lactation:

As a rule, diuretic drugs are not used during pregnancy.

Do not use these drugs for the treatment of physiological edema during pregnancy, tk. they can cause fetoplacental ischemia and can lead to impaired fetal development.

Indapamide is excreted in breast milk. If treatment with Indapamide retard is necessary during lactation, then breastfeeding should be discontinued.

Dosing and Administration:

Inside, 1 tablet a day, preferably in the morning. The tablet should be swallowed whole, not liquid, squeezed with water.

Increasing the dose does not lead to an increase in antihypertensive effects, but enhances the diuretic effect.

Elderly patients

In elderly patients, plasma concentrations of creatinine should be monitored, taking into account age, body weight and sex.

Indapamide retard can be used in elderly patients with normal or slightly impaired renal function.

Side effects:

Most adverse reactions are dose-dependent.

From the digestive system: nausea, anorexia, dryness of the oral mucosa, gastralgia, vomiting, diarrhea, constipation, abdominal pain, impaired liver function, hepatic encephalopathy, hepatitis, increased activity of "liver" transaminases, pancreatitis.

On the part of the hematopoiesis system: hyperuricemia, hyperglycemia, hypokalemia, hypochloraemia, hyponatremia, hypomagnesemia, hypercalcemia, elevated plasma urea nitrogen, hypercreatininemia, glucosuria, thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.

Allergic reactions: skin rash, angioedema, urticaria, itching, toxic epidermal necrolysis, Stevens-Johnson syndrome, hemorrhagic vasculitis.

From the central nervous system: asthenia, nervousness, headache, dizziness, drowsiness, vertigo, insomnia, depression, fatigue, general weakness, malaise, muscle spasm, paresthesia, tension, irritability, anxiety.

From the respiratory system: cough, pharyngitis, sinusitis, rhinitis.

From the cardiovascular system: fainting, marked decrease in blood pressure, changes in the electrocardiogram (ECG) (characteristic of hypokalemia), lengthening of the interval QT on an electrocardiogram, an arrhythmia, an arrhythmia of type "pirouette", sensation of palpitation.

From the urinary system: frequent infections, nocturia, polyuria, renal failure.

Other: exacerbation of the systemic lupus erythematosus, photosensitivity reaction.

Overdose:

Indapamide even in doses up to 40 mg, i.e. 27 times more than the therapeutic dose does not have a toxic effect.

Signs of acute drug poisoning are primarily associated with a violation of water electrolyte balance (hyponatremia, hypokalemia). From clinical symptoms of overdose, nausea, vomiting, lowering of blood pressure, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria leading to anuria (due to hypovolemia) may occur.

Treatment: gastric lavage, and / or reception of activated charcoal, followed by restoration of the water-electrolyte balance. There is no specific antidote.

Interaction:

UNEXPECTED COMBINATIONS

- Lithium preparations

With simultaneous use of indapamide and lithium preparations, an increase in the concentration of lithium in blood plasma can be observed due to a decrease in its excretion, accompanied by the appearance of signs of an overdose. If necessary, diuretic drugs can be prescribed in combination with lithium preparations, while carefully selecting the dose of drugs, constantly monitoring the lithium content in blood plasma.

COMBINATIONS REQUIRING A SPECIAL CAUTION

- Drugs that can cause arrhythmia such as "pirouette"

antiarrhythmic drugs IA class (quinidine, hydroquinidine, disopyramide);
antiarrhythmic drugs of III class (amiodarone, dofetilide, ibutilide), sotalol;
some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);
other: bepridil, cisapride, difemanyl, erythromycin (iv), halofantrine, misolastine, pentamidine, sparfloxacin, moxifloxacin, astemizole, wincamine (w / w).

Increased risk of ventricular arrhythmias, especially arrhythmias such as pirouettes (risk factor - hypokalemia).

It is necessary to determine the content of potassium in blood plasma and, if necessary, to adjust before the initiation of combined therapy with indapamide and the above drugs. It is necessary to monitor the clinical condition of the patient, control the content of plasma electrolytes, ECG,

Patients with hypokalemia should be prescribed drugs that do not cause arrhythmia such as "pirouette".

- Non-steroidal anti-inflammatory drugs (for systemic use), including selective inhibitors of cyclooxygenase-2 (COX-2), high doses of salicylates (≥ 3 g / day)

It is possible to reduce the antihypertensive effect of indapamide. With a significant loss of fluid, acute renal failure may develop (due to a decrease in glomerular filtration). Patients need to compensate for fluid loss and at the beginning of treatment carefully monitor kidney function.

- Angiotensin converting enzyme (ACE) inhibitors

The use of ACE inhibitors in patients with a reduced content of sodium ions in the blood (especially patients with renal artery stenosis) is accompanied by a risk of sudden arterial hypotension and / or acute renal failure.

Patients with arterial hypertension and possibly reduced, due to the intake of diuretics, the content of sodium ions in the blood plasma is necessary:

- 3 days before the start of treatment with an ACE inhibitor, stop taking diuretics. In the future, if necessary, the reception of diuretics can be resumed;

- or initiate therapy with an ACE inhibitor from low doses, followed by a gradual increase in dose, if necessary.

When chronic heart failure treatment with ACE inhibitors should be started with low doses with a possible preliminary reduction in the dose of diuretics.

In all cases in the first week of taking ACE inhibitors in patients, it is necessary to monitor the kidney function (the concentration of creatinine in the blood plasma).

- Other drugs that can cause hypokalemia: amphotericin B (IV), gluco- and mineralocorticosteroids (with systemic application), tetracosactide, laxatives, stimulating bowel motility

Increased risk of hypokalemia (additive effect).

It is necessary to regularly monitor the potassium content in the blood plasma, if necessary, correction. Particular attention should be given to patients who simultaneously receive cardiac glycosides.

It is recommended to use laxatives that do not stimulate intestinal motility.

- Baclofen

There is an increase in the hypotensive effect. Patients need to compensate for fluid loss, and, at the beginning of treatment, carefully monitor kidney function.

- Cardiac glycosides

Hypokalemia increases the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, it is necessary to monitor the potassium content in the blood plasma, the parameters of the ECG, and, if necessary, adjust the therapy.

COMBINATIONS OF PREPARATIONS THAT REQUIRE ATTENTION

- Potassium-sparing diuretics (amiloride, spironolactone, triamterene)

Combination therapy with indapamide and potassium-sparing diuretics suitable for some patients, but it does not exclude the possibility of hypokalemia (especially in patients with diabetes and renal insufficiency) or hyperkalemia.

It is necessary to monitor the potassium content in the blood plasma, the parameters of the ECG and, if necessary, adjust the therapy.

- Metformin

Functional renal failure, which can occur against the background of diuretics, especially "loop", with the simultaneous use of metformin increases the risk of lactic acidosis.

Do not assign metformin, if the creatinine concentration exceeds 15 mg / L (135 μmol / L) in men and 12 mg / L (110 μmol / L) in women.

- Iodine-containing contrast agents

Dehydration of the body against the background of taking diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents.

Before using iodine-containing contrast agents, patients must compensate for fluid loss.

- Tricyclic antidepressants, antipsychotics (antipsychotics)

Preparations of these classes increase the antihypertensive effect of indapamide and increase the risk of orthostatic hypotension (additive effect).

- Salts of calcium

With simultaneous application, it is possible to develop hypercalcemia due to a decrease in excretion of calcium ions by the kidneys.

- Cyclosporin, tacrolimus

It is possible to increase the concentration of creatinine in the blood plasma without changing the concentration of circulating cyclosporine, even with a normal content of liquid and sodium ions.

- Corticosteroids, tetracosactide (with systemic application)

Reduction of hypotensive effect (fluid retention and sodium ions as a result of corticosteroids).

Special instructions:

Dysfunction of the liver

With the use of thiazide and thiazide-like diuretics in patients with impaired hepatic function, it is possible to develop hepatic encephalopathy, especially in the case of disturbance of the water-electrolyte balance. In this case, the taking of diuretics should be stopped immediately.

Photosensitivity reaction

Against the background of taking thiazide and thiazide-like diuretics, cases of development of photosensitivity reactions were reported (see "Side effect"). In the case of developing photosensitivity reactions against the background of taking the drug should stop treatment.

If it is necessary to continue therapy with diuretics, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Water-electrolyte balance

- Content of sodium ions in blood plasma

Before the start of treatment it is necessary to determine the content of sodium ions in the blood plasma. Against the background of taking the drug should regularly monitor this figure. All diuretics can cause hyponatremia, which sometimes leads to extremely serious consequences. It is necessary to regularly monitor the content of sodium ions, since initially a decrease in the sodium content in the blood plasma may not be accompanied by the appearance of pathological symptoms.The most thorough control of the sodium ion content is indicated for patients with cirrhosis of the liver and elderly patients (see "Side effect" and "Overdose" sections).

- The content of potassium ions in the blood plasma

With thiazide and thiazide-like diuretics, the main risk is a sharp decrease in potassium in the blood plasma and the development of hypokalemia. It is necessary to avoid the risk of hypokalemia (<3.4 mmol / L) in patients of the following categories: elderly, debilitated or receiving concomitant drug therapy with other antiarrhythmic drugs and drugs that may increase the interval QT, patients with cirrhosis of the liver, peripheral edema or ascites, ischemic heart disease, heart failure.

Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias. In addition, the high-risk group includes patients with an increased interval QT, it does not matter whether this increase is due to innate causes or effects of drugs.

Hypokalemia, as well as bradycardia, is a condition,contributing to the development of severe arrhythmias and, especially, pirouette-type arrhythmias, which can lead to death. In all the cases described above, it is necessary to regularly monitor the potassium content in the blood plasma. The first measurement of the content of potassium ions in the blood should be carried out within the first week after the start of treatment. When hypokalemia occurs, appropriate treatment should be prescribed.

- Calcium in the blood plasma

It should be borne in mind that thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the calcium content in the blood plasma. Expressed hypercalcemia may be a consequence of previously not diagnosed hyperparathyroidism.

It is necessary to cancel the reception of diuretic drugs before the study of the function of parathyroid glands.

- The content of glucose in the blood plasma

It is necessary to monitor the concentration of glucose in the blood in patients with diabetes mellitus, especially in the presence of hypokalemia.

Uric acid

In patients with gout, the frequency of seizures may increase or the course of gout may worsen.

Diuretic drugs and kidney function

Thiazide and thiazide-like diuretics are effective only in patients with normal or slightly impaired renal function (creatinine plasma concentrations in adults below 25 mg / L or 220 μmol / L). In elderly patients, the normal concentration of creatinine in the blood plasma is calculated taking into account age, body weight and sex.

It should be borne in mind that at the beginning of treatment, patients may experience a decrease in the glomerular filtration rate due to hypovolemia, which in turn is caused by loss of fluid and sodium ions on the background of taking diuretic drugs. As a consequence, the blood plasma can increase the concentration of urea and creatinine. If the function of the kidneys is not impaired, such temporary functional renal failure usually passes without consequences, but with the existing renal failure, the patient's condition may worsen.

Athletes

The active substance, which is part of the preparation Indapamid retard, can give a positive result in the conduct of doping control in athletes.

Effect on the ability to drive transp. cf. and fur:The action of substances that make up the preparation Indapamid retard, does not lead to a disturbance of psychomotor reactions. However, in some patients, in response to a drop in blood pressure, various individual reactions may develop, especially at the onset of therapy or when other antihypertensive agents are added to the therapy. In this case, the ability to drive vehicles or other mechanisms can be reduced.

Form release / dosage:

Tablets of prolonged action, film-coated, 1.5 mg.

Packaging:

By 10, 20, or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

According to 1, 2, 3, 6 contour cell packs of 10 tablets or 1, 2, 3, 4 contour packs of 20 or 30 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-002529

Date of registration:13.03.2012

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Representation: & nbspCANONFARMA PRODUCTION CJSC CANONFARMA PRODUCTION CJSC Russia

Information update date: & nbsp16.10.2015

Illustrated instructions

Instructions

Indapamide retard (Indapamide retard)